Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach
Cancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (C...
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doaj-bf897c740d3443aba1c3d17ecf6f3e992021-09-24T14:41:25ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.18246421824642Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approachAna María Hurtado López0Tzu Hua Chen-Liang1María Zurdo2Salvador Carrillo-Tornel3Joaquín Panadero4Eduardo José Salido5Victor Beltrán6Begoña Muiña7MariLuz Amigo8Noelia Navarro-Villamor9Rosa Cifuentes10Inés Calabria11Ana Isabel Antón12Raúl Teruel13Manuel Muro14Vicente Vicente15Andrés Jerez16Hospital Universitario Morales Meseguer, IMIBHospital Universitario Morales Meseguer, IMIBHospital Universitario Morales Meseguer, IMIBHospital Universitario Morales Meseguer, IMIBHealth Research Institute La FeVirgen De La Arrixaca University HospitalH Virgen Del CastilloHospital Rafael MéndezHospital Universitario Morales Meseguer, IMIBIMIB-ArrixacaHospital Universitario Morales Meseguer, IMIBHealth Research Institute La FeIMIB-ArrixacaHospital Universitario Morales Meseguer, IMIBHospital Clínico Universitario Virgen De La ArrixacaHospital Universitario Morales Meseguer, IMIBHospital Universitario Morales Meseguer, IMIBCancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) is a prerequisite for downstream immune target-discovery projects. In this study, we take advantage of the use of azacitidine to treat high-risk MDS and CMML to draw the CTAs landscape, before and after treatment, using an ad hoc targeted RNA sequencing (RNA-seq) design for this group of low transcript genes. In 19 patients, 196 CTAs were detected at baseline. Azacitidine did not change the number of CTAs expressed, but it significantly increased or decreased expression in nine and five CTAs, respectively. TFDP3 and DDX53, emerged as the main candidates for immunotherapeutic targeting, as they showed three main features: i) a significant derepression on day +28 of cycle one in those patients who achieved complete remission with hypomethylating treatment (FC = 6, p = .008; FC = 2.1, p = .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognized TFDP3 and DDX53 reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine.http://dx.doi.org/10.1080/2162402X.2020.1824642cancer testis antigensazacitidinemyelodysplastic syndromest-cell response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana María Hurtado López Tzu Hua Chen-Liang María Zurdo Salvador Carrillo-Tornel Joaquín Panadero Eduardo José Salido Victor Beltrán Begoña Muiña MariLuz Amigo Noelia Navarro-Villamor Rosa Cifuentes Inés Calabria Ana Isabel Antón Raúl Teruel Manuel Muro Vicente Vicente Andrés Jerez |
spellingShingle |
Ana María Hurtado López Tzu Hua Chen-Liang María Zurdo Salvador Carrillo-Tornel Joaquín Panadero Eduardo José Salido Victor Beltrán Begoña Muiña MariLuz Amigo Noelia Navarro-Villamor Rosa Cifuentes Inés Calabria Ana Isabel Antón Raúl Teruel Manuel Muro Vicente Vicente Andrés Jerez Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach OncoImmunology cancer testis antigens azacitidine myelodysplastic syndromes t-cell response |
author_facet |
Ana María Hurtado López Tzu Hua Chen-Liang María Zurdo Salvador Carrillo-Tornel Joaquín Panadero Eduardo José Salido Victor Beltrán Begoña Muiña MariLuz Amigo Noelia Navarro-Villamor Rosa Cifuentes Inés Calabria Ana Isabel Antón Raúl Teruel Manuel Muro Vicente Vicente Andrés Jerez |
author_sort |
Ana María Hurtado López |
title |
Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach |
title_short |
Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach |
title_full |
Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach |
title_fullStr |
Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach |
title_full_unstemmed |
Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach |
title_sort |
cancer testis antigens in myelodysplastic syndromes revisited: a targeted rna-seq approach |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2020-01-01 |
description |
Cancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) is a prerequisite for downstream immune target-discovery projects. In this study, we take advantage of the use of azacitidine to treat high-risk MDS and CMML to draw the CTAs landscape, before and after treatment, using an ad hoc targeted RNA sequencing (RNA-seq) design for this group of low transcript genes. In 19 patients, 196 CTAs were detected at baseline. Azacitidine did not change the number of CTAs expressed, but it significantly increased or decreased expression in nine and five CTAs, respectively. TFDP3 and DDX53, emerged as the main candidates for immunotherapeutic targeting, as they showed three main features: i) a significant derepression on day +28 of cycle one in those patients who achieved complete remission with hypomethylating treatment (FC = 6, p = .008; FC = 2.1, p = .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognized TFDP3 and DDX53 reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine. |
topic |
cancer testis antigens azacitidine myelodysplastic syndromes t-cell response |
url |
http://dx.doi.org/10.1080/2162402X.2020.1824642 |
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